AJP - Renal Physiology, Vol 259, Issue 6 971-F976, Copyright © 1990 by American Physiological Society
Ontogeny of DA1 receptor-adenylate cyclase coupling in proximal convoluted tubules
S. Kinoshita and R. A. Felder
Department of Pediatrics and Child Health, Kurume University School of Medicine, Japan.
The natriuretic effect of dopamine (DA) is less in younger than in older
animals. The natriuretic (DA) is less in younger than in older animals. The
natriuretic effect of DA is due in part to occupation of renal tubular DA1
receptors, which are most abundant in the proximal convoluted tubule (PCT).
However, it has not been determined whether ontogenic differences in
DA1-receptor density, affinity, or coupling to intracellular second
messengers are involved in the reduced natriuretic effect of DA in the
young animal. We therefore studied the DA1 receptor by radioligand binding
with the DA1 antagonist 125I-SCH 23982 and the effect of DA1 agonists and
guanine nucleotides on adenylate cyclase (AC) activity in microdissected
PCT during development in Wistar-Kyoto rats (WKY). The dissociation
constant (Kd) and maximum receptor density (Bmax) were similar in all
groups (Kd, in nM: 11.9 +/- 0.7 at 3 wk, 10.6 +/- 0.4 at 8 wk, and 12.2 +/-
1.2 at 20 wk; Bmax, in fmol/mm PCT: 0.24 +/- 0.02 at 3 wk, 0.23 +/- 0.01 at
8 wk, and 0.24 +/- 0.01 at 20 wk). Basal AC activities were similar, and
forskolin (10(-5) M), which directly stimulates AC, increased AC activity
to a similar extent in all age groups. However, the DA1 agonists,
fenoldopam (10(-5) M) and SND-919-CL2 (10(-6) M), increased AC activity in
PCT to a greater extent in 20-wk-old (55 +/- 7%) than in 3-wk-old rats (27
+/- 1%).(ABSTRACT TRUNCATED AT 250 WORDS)
